Nerves in the Tumor Microenvironment: Origin and Effects

Wang, Wenjun; Li, Lingyu; Chen, Naifei; Niu, Chao; Li, Zhi; Hu, Jenny; Cui, Jiuwei

doi:10.3389/fcell.2020.601738

Cited by 58 publications

(79 citation statements)

References 137 publications

(276 reference statements)

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“…In adaptive immunity, activation of the β-AR signaling pathway significantly inhibited CD8 + T cell production, proliferation ( Nissen et al, 2018 ). β2-AR interacted with chemokine receptors CCR7 and CXCR4 to promote lymphocyte retention in lymph nodes; activation of β2ARs enhanced retention-promoting signaling through CCR7 and CXCR4, inhibiting lymphocyte export in lymph nodes ( Nakai et al, 2014 ; Wang W. et al, 2020 ). Those observations suggested interactions between the nerves and the immune cells, although direct evidence for this interaction has not been obtained.…”

Section: Nerves In Tumor Microenvironment Of Gastrointestinal Cancersmentioning

confidence: 99%

Non-immune Cell Components in the Gastrointestinal Tumor Microenvironment Influencing Tumor Immunotherapy

Zhang

Liu

et al. 2021

Front. Cell Dev. Biol.

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Interactions of genetic susceptibility factors, immune microenvironment, and microbial factors contribute to gastrointestinal tumorigenesis. The suppressive immune microenvironment reshaped by the tumors during gastrointestinal tumorigenesis directly contributes to T-cell depletion in tumor immunotherapy. Soluble factors secreted by tumor cells or stromal cells collectively shape the suppressive immune environment. Here, we reviewed the key factors in the gastrointestinal tumor microenvironment that influence tumor immunotherapy, focusing on the effects of fibroblasts, neuronal cells, soluble cytokines, exosomes, and the microbiome in tumor microenvironment. Research in this field has helped to identify more precise and effective biomarkers and therapeutic targets in the era of tumor immunotherapy.

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Section: Nerves In Tumor Microenvironment Of Gastrointestinal Cancersmentioning

confidence: 99%

Non-immune Cell Components in the Gastrointestinal Tumor Microenvironment Influencing Tumor Immunotherapy

Zhang

Liu

et al. 2021

Front. Cell Dev. Biol.

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“…At the tissue level, mRNA data from patient samples showed significantly more events of perineural invasion in the group with both high NMU and NMUR2 expression. Perineural invasion together with other types of invasion is a known mechanism of solid tumour dissemination [ 45 ] and refers to the invasion of the perineurium of large nerves by cancer cells, which is a prognostic factor of poor outcome in CRC [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Neuromedin U induces an invasive phenotype in CRC cells expressing the NMUR2 receptor

Przygodzka

Sochacka

Soboska

et al. 2021

J Exp Clin Cancer Res

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Background Successful colorectal cancer (CRC) therapy often depends on the accurate identification of primary tumours with invasive potential. There is still a lack of identified pathological factors associated with disease recurrence that could help in making treatment decisions. Neuromedin U (NMU) is a secretory neuropeptide that was first isolated from the porcine spinal cord, and it has emerged as a novel factor involved in the tumorigenesis and/or metastasis of many types of cancers. Previously associated with processes leading to CRC cell invasiveness, NMU has the potential to be a marker of poor outcome, but it has not been extensively studied in CRC. Methods Data from The Cancer Genome Atlas (TCGA) were used to analyse NMU and NMU receptor (NMUR1 and NMUR2) expression in CRC tissues vs. normal tissues, and real-time PCR was used for NMU and NMU receptor expression analysis. NMU protein detection was performed by immunoblotting. Secreted NMU was immunoprecipitated from cell culture-conditioned media and analysed by immunoblotting and protein sequencing. DNA demethylation by 5-aza-CdR was used to analyse the regulation of NMUR1 and NMUR2 expression. NMU receptor activity was monitored by detecting calcium mobilisation in cells loaded with fluo-4, and ERK1/2 kinase activation was detected after treatment with NMU or receptor agonist. Cell migration and invasion were investigated using membrane filters. Integrin expression was evaluated by flow cytometry. Results The obtained data revealed elevated expression of NMU and NMUR2 in CRC tissue samples and variable expression in the analysed CRC cell lines. We have shown, for the first time, that NMUR2 activation induces signalling in CRC cells and that NMU increases the motility and invasiveness of NMUR2-positive CRC cells and increases prometastatic integrin receptor subunit expression. Conclusions Our results show the ability of CRC cells to respond to NMU via activation of the NMUR2 receptor, which ultimately leads to a shift in the CRC phenotype towards a more invasive phenotype.

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“…Therefore, there is reason to believe that reprogrammed SCs can promote axon genesis and extend into the tumor body via their functions in the nerve regeneration process, which contributed to tumor innervation [ 10 , 18 , 32 ]. This increased neurogenesis is accompanied by an increase in the production of neurotransmitters that facilitate the proliferation and spread of cancer, which ultimately further promotes tumor development [ 10 , 66 ]. In addition, these neurotrophic factors secreted by SCs in the above process are the key molecules that promote PNI [ 33 , 38 , 41 ].…”

Section: Scs In the “Tumor-nerve Niche”mentioning

confidence: 99%

Schwann Cells in the Tumor Microenvironment: Need More Attention

Sun

Chen

2022

Journal of Oncology

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The tumor microenvironment (TME), which is composed of various cell components and signaling molecules, plays an important role in the occurrence and progression of tumors and has become the central issue of current cancer research. In recent years, as a part of the TME, the peripheral nervous system (PNS) has attracted increasing attention. Moreover, emerging evidence shows that Schwann cells (SCs), which are the most important glial cells in the PNS, are not simply spectators in the TME. In this review article, we focused on the up-to-date research progress on SCs in the TME and introduced our point of view. In detail, we described that under two main tumor-nerve interaction patterns, perineural invasion (PNI) and tumor innervation, SCs were reprogrammed and acted as important participants. We also investigated the newest mechanisms between the interactions of SCs and tumor cells. In addition, SCs can have profound impacts on other cellular components in the TME, such as immune cells and cancer-associated fibroblasts (CAFs), involving immune regulation, tumor-related pain, and nerve remodeling. Overall, these innovative statements can expand the scope of the TME, help fully understand the significant role of SCs in the tumor-nerve-immune axis, and propose enlightenments to innovate antitumor therapeutic methods and future research.

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Nerves in the Tumor Microenvironment: Origin and Effects

Cited by 58 publications

References 137 publications

Non-immune Cell Components in the Gastrointestinal Tumor Microenvironment Influencing Tumor Immunotherapy

Non-immune Cell Components in the Gastrointestinal Tumor Microenvironment Influencing Tumor Immunotherapy

Neuromedin U induces an invasive phenotype in CRC cells expressing the NMUR2 receptor

Schwann Cells in the Tumor Microenvironment: Need More Attention

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